Project Summary/Abstract Pediatric chronic pain is a serious public health problem resulting in high levels of healthcare utilization and disability. The physical and psychological consequences associated with chronic pain impact overall health and can predispose the development of adult chronic pain. Specifically, there has been an inadequate amount of research conducted on pediatric persistent postsurgical pain (PPP), which is urgently required given that over 5 million children undergo surgery each year and 25% of adults presenting to chronic pain clinics identify surgery as the antecedent. The proposed translational research project utilizes animal models, humans, genetics, and psychophysiological techniques to enhance our understanding of these mechanisms. The long- term goal of this K23 award is for the candidate to establish an independent translational research career aimed at developing mechanistically based behavioral interventions. The intent of the proposed project is to develop an animal model exploring how gene-environmental interactions, age, and biological sex contribute to pre- and post surgical pain thresholds, which will serve as a first step to functionally assaying genetic mechanisms we hope to discover in the gene association arm of our human studies. The human arm of this project is two-fold; examining the role of childhood stress and genetic pain risk on current pain and functioning in a large cohort of adult surgical patients, as well as continuing an IRB-approved study examining the sensory, psychosocial, and genetic predictors of PPP and related functional disability in pediatric patients with either idiopathic scoliosis undergoing spinal fusion surgery or developmental dysplasia of the hip undergoing hip osteotomy. This population was selected as a model condition because these are orthopedic conditions affecting children, the children are otherwise healthy, and both surgeries are quite invasive and complex with our research indicating that that a high proportion of these patients go onto to develop moderate to severe pain after surgery. The primary training objective is to acquire expertise in pain genetics, animal models, and translational research. The candidate will accomplish this through: 1) mentorship in a clinical/research environment, 2) hands-on training in animal models and genetics by the candidate's sponsor and co-sponsors complemented by didactics in genetics and advanced statistics, and 3) execution of the proposed research plan. These studies will provide the necessary data to inform the development of an R01 to focus on an epigenetic model to identify study genes, which markedly alter the risk profile for PPP and which will inform the development of new drug targets and behavioral interventions for those at greatest risk.